Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy

To evaluate the safety and tolerability of tree nut (cashew or pistachio, walnut or pecan, hazelnut, almond, and macadamia nut) oral immunotherapy (TN-OIT) among preschoolers with TN allergy in the real world relative to peanut oral immunotherapy, which has previously been shown to be safe and effective in preschoolers with peanut allergy.

This study included 92 preschoolers (ages 9–70 months) with TN allergy characterized by clinical reaction consistent with an IgE-mediated reaction and either a skin prick test greater than or equal to 3 mm or TN-specific IgE greater than or equal to 0.35 kU/mL or TN-specific IgE greater than or equal to 5 kU/mL with no prior TN ingestion.

Participants underwent TN-OIT using either TN meal or flour compounded into capsules or TN milk with starting doses ranging from 1 to 10 mg of TN protein, increasing every 2 to 4 weeks to a maintenance dose of 300 mg of TN protein. Symptoms and reaction management were reported by caregivers.

Among the 92 preschoolers who participated in TN-OIT, 88 (95.6%) achieved maintenance and 4 (4.3%) discontinued the treatment. Multifood TN-OIT was used in 14.1% of patients with 2 (10.8%) or 3 (3.3%) TNs. During the course of the treatment, there were 35 (38%) grade 1 reactions and 30 (32.6%) grade 2 reactions (graded using the modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System, with adaptations for infants). There were no grade 3 or 4 reactions. Two grade 2 reactions resulted in epinephrine use and 1 participant was evaluated in the emergency department. There were no diagnoses of eosinophilic esophagitis.

This study shows that TN-OIT can be safely and effectively conducted in the preschool population with expected mild reactions and side effects similar to those seen among preschoolers undergoing peanut oral immunotherapy.

Nearly 5% of the world’s population may be allergic to TN and the allergy is infrequently outgrown. In the context of shared decision making, treatment options to decrease risk of anaphylaxis with accidental TN exposure are needed. Food OIT has been shown to be safe and effective in the real-world setting.

This study advances our understanding of real-world OIT in the preschool setting to TNs.

Importantly, OIT should be viewed as a patient-sensitive treatment consideration that may be most effective in younger children. Like all therapies, OIT has risks and benefits.

Although OIT benefits may include protection from accidental exposures and, for some patients, the ability to consume the culprit allergen in the diet, the protection afforded by OIT can be lost with poor adherence to treatment or failure to regularly consume the allergen when a state of desensitization is achieved. It is unclear if OIT results in lasting tolerance, but some patients may experience sustained unresponsiveness to their food allergen over time. Importantly, preschool OIT should only be considered in partnership with a clinician with appropriate training and expertise in the management of pediatric food allergy.